The central objective of this proposal is to better understand the independent and interdependent roles of vitamin D (D) metabolites and parathyroid hormone (PTH) in normal and chronically uremic dogs. The first protocol will highlight the responses of normal dogs to two diets widely varying in calcium content. Circulating D metabolites and iPTH will be measured and classic metabolic balance studies performed for calcium, phosphorus and magnesium. The renal and bone response to PTH infusions will be compared during the two diets. To assess the degree to which calcium homeostasis remains operative in chronic uremia, the dogs will be rendered chronically uremic and the above study repeated. This phase of the study will investigate the ability of chronically uremic hyperparathyroid dogs to adapt to changes in calcium intake. Finally, we will explore the integrity of the calcium homeostatic axis with low and high calcium intakes in uremic dogs rendered euparathyroid with a restricted phosphorus intake. This final phase will test the hypothesis that many of the defects in calcium homeostasis and D metabolism are secondary to an unfavorable metabolic milieu and not an absolute reduction in nephron mass.